Congenital heart defects occur in humans involving the malformation frequently of the ventricular septums. The cause of such abnormality is largely obscured. The development of an animal model to study congenital heart defects will provide an experimental approach to this important, yet unresolved, problem. Recent studies from our laboratory on the effects of 6-hydroxydopamine (6-OHDA) has provided leads to study congenital heart defects, particularly the ventricular septal lesions. Evidence obtained thus far showed severe embryotoxicity of the heart following treatment with 6-OHDA. We have observed gross morphologic, microscopic and ultrastructural defects, as well as biochemical changes showing a depletion of norepinephrine level. The overall objective of this proposal is to develop a reliable animal model of inducing congenital malformations of the heart using 6-OHDA and to elucidate the role of the autonomic nervous system, namely the adrenergic and cholinergic systems which may play in the development of the heart, and the embryotoxicity of 6-OHDA. Both biochemical and morphological including ultrastructural techniques will be used. The synthesis of norepinephrine and acetylcholine from labeled tyrosine and choline respectively, and the incorporation of labeled protein and the enzymes involved in the synthesis of these transmitters (tyrosine hydroxylase, dopadecarboxylase and choline acetyltransferase) will be measured. These studies will help to identify the neuronal role in cardiac development and teratogenicity of 6-OHDA.